Project Summary: This research addresses a fundamental question in cell biology: How do cells detect mechanical stress in the actin cytoskeleton? The internal cytoskeletal tension is modulated by the mechanical properties of its external environment. Cytoskeletal tension can be an internal representation the mechanical properties of its local environment that can be ?read? by the biochemical machinery. In fact proteins can be stretched by mechanical forces to reveal new binding sites, the recognition of these newly revealed binding sites by ?sensor? proteins is one possible way of detecting mechanical information. The LIM superfamily represents a large number of putative mechanosensitive cellular proteins that detect stress by a completely unknown mechanism. I aim to identify the sequence determinants within the LIM domain responsible for detection of mechanical stress in the actin cytoskeleton. I then aim to discover the molecular mechanisms by which LIM domain proteins detect this stress, including identifying what LIM domains bind to and the nature of the deformation in the actin cytoskeleton. Revealing the mechanism of how a single member of this family detects cytoskeletal deformations will likely be generalizable to a large number of proteins. This will also drive future research involving how mechanosensitivity of each LIM protein is tuned and specificity achieved.